Originally, we had proposed that the level, intensity, and balance of remodeling activity in the skeleton were governed by the relative strengths of "osteolytic" and "osteogenic" stimuli. A functionally "appropriate" level of bone mass, therefore, would simply result from a mechanically engendered osteogenic stimulus countering a net "systemic" drive towards resorption. If the functional stimulus were removed or weakened (as in immobilization), or if the systemic stimulus were strengthened (as in calcium insufficiency or endocrinopathy), bone mass would decline, progressively increasing the individual's susceptibility to fracture. New observations, however, have led to a refinement of this hypothesis. Indeed, it is now apparent that the skeleton's ability to either perceive, or respond to, "positive" functional stimuli is markedly attenuated while the skeleton concurrently suffers from a state of systemic "imbalance". The osteogenic rules which govern Wolff's Law in a "normal" skeleton are not sufficient to counteract the osteopenia associated with systemic disorders. The objective of this five year proposal is to evaluate the relative potential of mechanical stimuli to inhibit or reverse the osteopenia associated with four "negative balance" systemic states: 1) aging; 2) disuse; 3) nutritional deficiency; and 4) endocrinopathy. As the mechanical state of the functionally isolated turkey ulna preparation can be readily controlled, this model will be exploited in this protocol. Four distinct experimental populations of turkeys will be created, each representative of one of these systemic types. The relative remodeling response in each of the four systemic states to three specific mechanical regimens will be established from post- mortem histology, microradiography, and the distribution of flourescent labels given over the experimental period. The clinical relevance of this study is targetted towards the prevention and/or reversal of bone loss in the immobilized patient and the aging post-menopausal population. Our preliminary experiments reflect a complex, rather than a simple, relationship between the mechanical environment and the systemic state of the organism. The proposed experiments are designed to elaborate on these observations, and to explore those aspects of the mechanical signal which positively influence skeletal mass, even while under a systemic state of "negative imbalance".